Abstract
Over the last decade it has become increasingly clear that the Sm-like (Lsm) protein Hfq, initially identified as a host factor required for Qβ bacteriophage replication, acts as a global post-transcriptional regulator in enterobacteria (reviewed in Valentin-Hansen et al. 2004; Storz et al. 2004; Gottesman et al. 2006; Vogel 2009a). Most of our current knowledge derives from detailed studies of small regulatory RNAs (sRNAs) in Escherichia coli and Salmonella. In particular, Hfq has been implicated in the regulation of translation and stability of an increasing number of mRNAs and its action has been shown to be intimately linked with the activity of a family of chromosomally encoded sRNAs that function in post-transcriptional control by base-pairing with cognate target mRNAs. Hfq associates with both regulatory RNAs and target RNA(s) and is required for proper riboregulation in enterobacteria. The importance of Hfq is further underscored by its multiple roles in bacterial physiology, including stress responses, bacteriocin production, nitrogen fixation, symbiosis, motility, quorum sensing and virulence of various bacterial pathogens (for reviews of Hfq activities see Vassilieva and Garber 2002; Valentin-Hansen et al. 2004; Dienst et al. 2008; Fröhlich and Vogel 2009). Here I will focus on novel findings about Hfq, its structure, RNA-binding mechanisms and mode of action in riboregulation and mRNA decay.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Achsel T, Stark H, Lührmann R (2001) The Sm domain is an ancient RNA-binding motif with oligo(U) specificity. Proc Natl Acad Sci U S A 98:3685–3689
Aiba H (2007) Mechanism of RNA silencing by Hfq-binding small RNAs. Curr Opin Microbiol 10:134–139
Anderson KL, Dunman PM (2009) Messenger RNA Turnover Processes in Escherichia coli, Bacillus subtilis, and Emerging Studies in Staphylococcus aureus. Int J Microbiol 2009:525491
Arluison V, Folichon M, Marco S, Derreumaux P, Pellegrini O, Seguin J, Hajnsdorf E, Regnier P (2004) The C-terminal domain of Escherichia coli Hfq increases the stability of the hexamer. Eur J Biochem 271:1258–1265
Arluison V, Hohng S, Roy R, Pellegrini O, Regnier P, Ha T (2007) Spectroscopic observation of RNA chaperone activities of Hfq in post-transcriptional regulation by a small non-coding RNA. Nucleic Acids Res 35:999–1006
Attia AS, Sedillo JL, Wang W, Liu W, Brautigam CA, Winkler W, Hansen EJ (2008) Moraxella catarrhalis expresses an unusual Hfq protein. Infect Immun 76:2520–2530
Beggs J (2005) Lsm proteins and RNA processing. Biochem Soc Trans 33:433–438
Bøggild A, Overgaard M, Valentin-Hansen P, Brodersen DE (2009) Cyanobacteria contain a structural homologue of the Hfq protein with altered RNA-binding properties. FEBS J 276:3904–3915
Bohn C, Rigoulay C, Bouloc P (2007) No detectable effect of RNA-binding protein Hfq absence in Staphylococcus aureus. BMC Microbiol 7:10
Boysen A, Møller-Jensen J, Kallipolitis B, Valentin-Hansen P, Overgaard M (2010) Translational regulation of gene expression by an anaerobically induced small non-coding RNA in Escherichia coli. J Biol Chem 285:10690–10702
Brennan RG, Link TM (2007) Hfq structure, function and ligand binding. Curr Opin Microbiol 10:125–133
Brescia CC, Mikulecky PJ, Feig AL, Sledjeski DD (2003) Identification of the Hfq-binding site on DsrA RNA: Hfq binds without altering DsrA secondary structure. RNA 9:33–43
Carmichael GG (1975) Isolation of bacterial and phage proteins by homopolymer RNA-cellulose chromatography. J Biol Chem 250:6160–6167
Chevalier C, Boisset S, Romilly C, Masquida B, Fechter P, Geissmann T, Vandenesch F, Romby P (2010) Staphylococcus aureus RNAIII binds to two distant regions of coa mRNA to arrest translation and promote mRNA degradation. PLoS Pathog 6:e1000809
Christiansen JK, Larsen MH, Ingmer H, Søgaard-Andersen L, Kallipolitis BH (2004) The RNA-binding protein Hfq of Listeria monocytogenes: role in stress tolerance and virulence. J Bacteriol 186:3355–3362
Christiansen JK, Nielsen JS, Ebersbach T, Valentin-Hansen P, Søgaard-Andersen L, Kallipolitis BH (2006) Identification of small Hfq-binding RNAs in Listeria monocytogenes. RNA 12:1383–1396
Cooper M, Johnston LH, Beggs JD (1995) Identification and characterization of Uss1p (Sdb23p): a novel U6 snRNA-associated protein with significant similarity to core proteins of small nuclear ribonucleoproteins. EMBO J 14:2066–2075
Davis BM, Waldor MK (2007) RNase E-dependent processing stabilizes MicX, a Vibrio cholerae sRNA. Mol Microbiol 65:373–385
de Haseth PL, Uhlenbeck OC (1980a) Interaction of Escherichia coli host factor protein with Q beta ribonucleic acid. Biochemistry 19:6146–6151
de Haseth PL, Uhlenbeck OC (1980b) Interaction of Escherichia coli host factor protein with oligoriboadenylates. Biochemistry 19:6138–6146
Deana A, Belasco JG (2005) Lost in translation: the influence of ribosomes on bacterial mRNA decay. Genes Dev 19:2526–2533
Dienst D, Dühring U, Mollenkopf HJ, Vogel J, Golecki J, Hess WR, Wilde A (2008) The cyanobacterial homologue of the RNA chaperone Hfq is essential for motility of Synechocystis sp. PCC 6803. Microbiology 154:3134–3143
Diestra E, Cayrol B, Arluison V, Risco C (2009) Cellular electron microscopy imaging reveals the localization of the Hfq protein close to the bacterial membrane. PLoS One 4:e8301
Figueroa-Bossi N, Valentini M, Malleret L, Fiorini F, Bossi L (2009) Caught at its own game: regulatory small RNA inactivated by an inducible transcript mimicking its target. Genes Dev 23:2004–2015
Folichon M, Arluison V, Pellegrini O, Huntzinger E, Regnier P, Hajnsdorf E (2003) The poly(A) binding protein Hfq protects RNA from RNase E and exoribonucleolytic degradation. Nucleic Acids Res 31:7302–7310
Franch T, Gerdes K (2000) U-turns and regulatory RNAs. Curr Opin Microbiol 3:159–164
Franco-Zorrilla JM, Valli A, Todesco M, Mateos I, Puga MI, Rubio-Somoza I, Leyva A, Weigel D, Garcia JA, Paz-Ares J (2007) Target mimicry provides a new mechanism for regulation of microRNA activity. Nat Genet 39:1033–1037
Fröhlich KS, Vogel J (2009) Activation of gene expression by small RNA. Curr Opin Microbiol 12:674–682
Galão RP, Chari A, ves-Rodrigues I, Lobao D, Mas A, Kambach C, Fischer U, Diez J (2010) LSm1-7 complexes bind to specific sites in viral RNA genomes and regulate their translation and replication. RNA 16:817–827
Geissmann T, Chevalier C, Cros MJ, Boisset S, Fechter P, Noirot C, Schrenzel J, Francois P, Vandenesch F, Gaspin C, Romby P (2009) A search for small noncoding RNAs in Staphylococcus aureus reveals a conserved sequence motif for regulation. Nucleic Acids Res 37:7239–7257
Geissmann TA, Touati D (2004) Hfq, a new chaperoning role: binding to messenger RNA determines access for small RNA regulator. EMBO J 23:396–405
Georg J, Vosz B, Scholz I, Mitschke J, Wilde A, Hess WR (2009) Evidence for a major role of antisense RNAs in cyanobacterial gene regulation. Mol Syst Biol 5
Gottesman S, McCullen CA, Guillier M, Vanderpool CK, Majdalani N, Benhammou J, Thompson KM, FitzGerald PC, Sowa NA, FitzGerald DJ (2006) Small RNA regulators and the bacterial response to stress. Cold Spring Harb Symp Quant Biol 71:1–11
Hajnsdorf E, Régnier P (2000) Host factor Hfq of Escherichia coli stimulates elongation of poly(A) tails by poly(A) polymerase I. Proc Natl Acad Sci U S A 97:1501–1505
Hermann H, Fabrizio P, Raker VA, Foulaki K, Hornig H, Brahms K, Lührmann H (1995) snRNP Sm proteins share two evolutionarily conserved sequence motifs which are involved in Sm protein-protein interactions. EMBO J 14:2076–2088
Jousselin A, Metzinger L, Felden B (2009) On the facultative requirement of the bacterial RNA chaperone, Hfq. Trends Microbiol 17:399–405
Kawamoto H, Koide Y, Morita T, Aiba H (2006) Base-pairing requirement for RNA silencing by a bacterial small RNA and acceleration of duplex formation by Hfq. Mol Microbiol 61:1013–1022
Khusial P, Plaag R, Zieve GW (2005) LSm proteins form heptameric rings that bind to RNA via repeating motifs. Trends Biochem Sci 30:522–528
Lease RA, Woodson SA (2004) Cycling of the Sm-like protein Hfq on the DsrA small regulatory RNA. J Mol Biol 344:1211–1223
Lee T, Feig AL (2008) The RNA binding protein Hfq interacts specifically with tRNAs. RNA 14:514–523
Link TM, Valentin-Hansen P, Brennan RG (2009) Structure of Escherichia coli Hfq bound to polyriboadenylate RNA. Proc Natl Acad Sci U S A 106:19292–19297
Liu Y, Wu N, Dong J, Gao Y, Zhang X, Mu C, Shao N, Yang G (2010) Hfq is a global regulator that controls the pathogenicity of Staphylococcus aureus. PLoS One 5:e13069
Lorenz C, Gesell T, Zimmermann B, Schoeberl U, Bilusic I, Rajkowitsch L, Waldsich C, von Haeseler A, Schroeder R (2010) Genomic SELEX for Hfq-binding RNAs identifies genomic aptamers predominantly in antisense transcripts. Nucleic Acids Res
Mandin P, Gottesman S (2009a) A genetic approach for finding small RNAs regulators of genes of interest identifies RybC as regulating the DpiA/DpiB two-component system. Mol Microbiol 72:551–565
Mandin P, Gottesman S (2009b) Regulating the regulator: an RNA decoy acts as an OFF switch for the regulation of an sRNA. Genes Dev 23:1981–1985
Massé E, Escorcia FE, Gottesman S (2003) Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli. Genes Dev 17:2374–2383
Mikulecky PJ, Kaw MK, Brescia CC, Takach JC, Sledjeski DD, Feig AL (2004) Escherichia coli Hfq has distinct interaction surfaces for DsrA, rpoS and poly(A) RNAs. Nat Struct Mol Biol 11: 1206–1214.
Mohanty BK, Maples VF, Kushner SR (2004) The Sm-like protein Hfq regulates polyadenylation dependent mRNA decay in Escherichia coli. Mol Microbiol 54:905–920
Moll I, Afonyushkin T, Vytvytska O, Kaberdin VR, Bläsi U (2003) Coincident Hfq binding and RNase E cleavage sites on mRNA and small regulatory RNAs. RNA 9:1308–1314
Møller T, Franch T, Højrup P, Keene DR, Bächinger HP, Brennan RG, Valentin-Hansen P (2002a) Hfq: a bacterial Sm-like protein that mediates RNA-RNA interaction. Mol Cell 9:23–30
Møller T, Franch T, Udesen C, Gerdes K, Valentin-Hansen P (2002b) Spot 42 RNA mediates discoordinate expression of the E. coli galactose operon. Genes Dev 16:1696–1706
Morita T, Maki K, Aiba H (2005) RNase E-based ribonucleoprotein complexes: mechanical basis of mRNA destabilization mediated by bacterial noncoding RNAs. Genes Dev 19:2176–2186
Morita T, Maki K, Yagi M, Aiba H (2008) Analyses of mRNA destabilization and translational inhibition mediated by Hfq-binding small RNAs. Methods Enzymol 447:359–378
Nielsen JS, Bøggild A, Andersen CB, Nielsen G, Boysen A, Brodersen DE, Valentin-Hansen P (2007) An Hfq-like protein in archaea: crystal structure and functional characterization of the Sm protein from Methanococcus jannaschii. RNA 13:2213–2223
Nielsen JS, Lei LK, Ebersbach T, Olsen AS, Klitgaard JK, Valentin-Hansen P, Kallipolitis BH (2010) Defining a role for Hfq in Gram-positive bacteria: evidence for Hfq-dependent antisense regulation in Listeria monocytogenes. Nucleic Acids Res 38:907–919
Nikulin A (2005) Structure of Pseudomonas aeruginosa Hfq protein. Acta Crystallogr D 61:141–146
Nordström K, Wagner EG (1994) Kinetic aspects of control of plasmid replication by antisense RNA. Trends Biochem Sci 19:294–300
Olsen AS, Møller-Jensen J, Brennan RG, Valentin-Hansen P (2010) C-terminally truncated derivatives of Escherichia coli Hfq are proficient in riboregulation. J Mol Biol 404:173–82
Opdyke JA, Kang JG, Storz G (2004) GadY, a small-RNA regulator of acid response genes in Escherichia coli. J Bacteriol 186:6698–6705
Overgaard M, Johansen J, Moller-Jensen J, Valentin-Hansen P (2009) Switching off small RNA regulation with trap-mRNA. Mol Microbiol 73:790–800
Pfeiffer V, Papenfort K, Lucchini S, Hinton JC, Vogel J (2009) Coding sequence targeting by MicC RNA reveals bacterial mRNA silencing downstream of translational initiation. Nat Struct Mol Biol 16:840–846
Rajkowitsch L, Schroeder R (2007) Dissecting RNA chaperone activity. RNA 13:2053–2060
Rasmussen AA, Johansen J, Nielsen JS, Overgaard M, Kallipolitis B, Valentin-Hansen P (2009) A conserved small RNA promotes silencing of the outer membrane protein YbfM. Mol Microbiol 72:566–577
Rasmussen AA, Eriksen M, Gilany K, Udesen C, Franch T, Petersen C, Valentin-Hansen P (2005) Regulation of ompA mRNA stability: the role of a small regulatory RNA in growth phase-dependent control. Mol Microbiol 58:1421–1429
Repoila F, Darfeuille F (2009) Small regulatory non-coding RNAs in bacteria: physiology and mechanistic aspects. Biol Cell 101:117–131
Romby P, Charpentier E (2010) An overview of RNAs with regulatory functions in gram-positive bacteria. Cell Mol Life Sci 67:217–237
Sauter C, Basquin J, Suck D (2003) Sm-like proteins in Eubacteria: the crystal structure of the Hfq protein from Escherichia coli. Nucleic Acids Res 31:4091–4098
Scheller N, Mina LB, Galao RP, Chari A, Gimenez-Barcons M, Noueiry A, Fischer U, Meyerhans A, Diez J (2009) Translation and replication of hepatitis C virus genomic RNA depends on ancient cellular proteins that control mRNA fates. Proc Natl Acad Sci U S A 106:13517–13522
Schilling D, Gerischer U (2009) The Acinetobacter baylyi Hfq gene encodes a large protein with an unusual C terminus. J Bacteriol 191:5553–5562
Schumacher MA, Pearson RF, Møller T, Valentin-Hansen P, Brennan RG (2002) Structures of the pleiotropic translational regulator Hfq and an Hfq-RNA complex: a bacterial Sm-like protein. EMBO J 21:3546–3556
Senear AW, Steitz JA (1976) Site-specific interaction of Qbeta host factor and ribosomal protein S1 with Qbeta and R17 bacteriophage RNAs. J Biol Chem 251:1902–1912
Séraphin B (1995) Sm and Sm-like proteins belong to a large family: identification of proteins of the U6 as well as the U1, U2, U4 and U5 snRNPs. EMBO J 14:2089–2098
Sittka A, Sharma CM, Rolle K, Vogel J (2009) Deep sequencing of Salmonella RNA associated with heterologous Hfq proteins in vivo reveals small RNAs as a major target class and identifies RNA processing phenotypes. RNA Biol 6:266–275
Sonnleitner E, Moll I, Bläsi U (2002) Functional replacement of the Escherichia coli hfq gene by the homologue of Pseudomonas aeruginosa. Microbiology-Sgm 148:883–891
Sonnleitner E, Napetschnig J, Afonyushkin T, Ecker K, Vecerek B, Moll I, Kaberdin VR, Blasi U (2004) Functional effects of variants of the RNA chaperone Hfq. Biochem Biophys Res Commun 323:1017–1023
Soper T, Mandin P, Majdalani N, Gottesman S, Woodson SA (2010) Positive regulation by small RNAs and the role of Hfq. Proc Natl Acad Sci U S A
Soper TJ, Woodson SA (2008) The rpoS mRNA leader recruits Hfq to facilitate annealing with DsrA sRNA. RNA 14:1907–1917
Storz G, Opdyke JA, Zhang A (2004) Controlling mRNA stability and translation with small, noncoding RNAs. Curr Opin Microbiol 7:140–144
Sun X, Wartell RM (2006) Escherichia coli Hfq binds A18 and DsrA domain II with similar 2∶1 Hfq6/RNA stoichiometry using different surface sites. Biochemistry 45:4875–4887
Sun XG, Zhulin I, Wartell RM (2002) Predicted structure and phyletic distribution of the RNAbinding protein Hfq. Nucl Acids Res 30:3662–3671
Toledo-Arana A, Dussurget O, Nikitas G, Sesto N, Guet-Revillet H, Balestrino D, Loh E, Gripenland J, Tiensuu T, Vaitkevicius K, Barthelemy M, Vergassola M, Nahori MA, Soubigou G, Regnault B, Coppee JY, Lecuit M, Johansson J, Cossart P (2009) The Listeria transcriptional landscape from saprophytism to virulence. Nature 459:950–956
Törö I, Thore S, Mayer C, Basquin J, Séraphin B, Suck D (2001) RNA binding in an Sm core domain: X-ray structure and functional analysis of an archaeal Sm protein complex. EMBO J 20:2293–2303
Tsui HCT, Leung HCE, Winkler ME (1994) Characterization of broadly pleiotropic phenotypes caused by an Hfq insertion mutation in Escherichia-coli-K-12. Mol Microbiol 13:35–49
Updegrove T, Wilf N, Sun X, Wartell RM (2008) Effect of Hfq on RprA-rpoS mRNA pairing: Hfq-RNA binding and the influence of the 5′ rpoS mRNA leader region. Biochemistry 47:11184–11195
Updegrove TB, Correia JJ, Galletto R, Bujalowski W, Wartell RM (2010) E. coli DNA associated with isolated Hfq interacts with Hfq’s distal surface and C-terminal domain. Biochim Biophys Acta 1799:588–96
Valentin-Hansen P, Eriksen M, Udesen C (2004) The bacterial Sm-like protein Hfq: a key player in RNA transactions. Mol Microbiol 51:1525–1533
Vassilieva IM, Garber MB (2002) The regulatory role of the Hfq protein in bacterial cells. Mol Biol 36:970–977
Vecerek B, Rajkowitsch L, Sonnleitner E, Schroeder R, Bläsi U (2008) The C-terminal domain of Escherichia coli Hfq is required for regulation. Nucleic Acids Res 36:133–143
Viegas SC, Arraiano CM (2008) Regulating the regulators: How ribonucleases dictate the rules in the control of small non-coding RNAs. RNA Biol 5:230–243
Vogel J (2009a) A rough guide to the non-coding RNA world of Salmonella. Mol Microbiol 71:1–11
Vogel J (2009b) An RNA trap helps bacteria get the most out of chitosugars. Mol Microbiol 73:737–741
Wagner EG (2009) Kill the messenger: bacterial antisense RNA promotes mRNA decay. Nat Struct Mol Biol 16:804–806
Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S (2001) Identification of novel small RNAs using comparative genomics and microarrays. Genes Dev 15:1637–1651
Waters LS, Storz G (2009) Regulatory RNAs in bacteria. Cell 136:615–628
Wilusz CJ, Wilusz J (2005) Eukaryotic Lsm proteins: lessons from bacteria. Nat Struct Mol Biol 12:1031–1036
Woese CR, Kandler O, Wheelis ML (1990) Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci U S A 87:4576–4579
Worrall JA, Gorna M, Crump NT, Phillips LG, Tuck AC, Price AJ, Bavro VN, Luisi BF (2008) Reconstitution and analysis of the multienzyme Escherichia coli RNA degradosome. J Mol Biol 382:870–883
Zhang A, Wassarman KM, Ortega J, Steven AC, Storz G (2002) The Sm-like Hfq protein increases OxyS RNA interaction with target mRNAs. Mol Cell 9:11–22
Zhang A, Wassarman KM, Rosenow C, Tjaden BC, Storz G, Gottesman S (2003) Global analysis of small RNA and mRNA targets of Hfq. Mol Microbiol 50:1111–1124
Ziolkowska K, Derreumaux P, Folichon M, Pellegrini O, Regnier P, Boni IV, Hajnsdorf E (2006) Hfq variant with altered RNA binding functions. Nucleic Acids Res 34:709–720
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag/Wien
About this chapter
Cite this chapter
Valentin-Hansen, P. (2012). Structure, Function and RNA Binding Mechanisms of the Prokaryotic Sm-like Protein Hfq. In: Regulatory RNAs in Prokaryotes. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0218-3_8
Download citation
DOI: https://doi.org/10.1007/978-3-7091-0218-3_8
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-0217-6
Online ISBN: 978-3-7091-0218-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)